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Aliases for HCN2 Gene

Aliases for HCN2 Gene

  • Hyperpolarization Activated Cyclic Nucleotide Gated Potassium And Sodium Channel 2 2 3 5
  • Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 2 2 3
  • Brain Cyclic Nucleotide-Gated Channel 2 3 4
  • BCNG-2 3 4
  • BCNG2 3 4
  • Potassium/Sodium Hyperpolarization-Activated Cyclic Nucleotide-Gated Channel 2 3
  • Hyperpolarization Activated Cyclic Nucleotide-Gated Potassium Channel 2 2
  • HAC-1 3

External Ids for HCN2 Gene

Previous HGNC Symbols for HCN2 Gene

  • BCNG2

Previous GeneCards Identifiers for HCN2 Gene

  • GC19P000641
  • GC19P000529
  • GC19P000540
  • GC19P000359

Summaries for HCN2 Gene

Entrez Gene Summary for HCN2 Gene

  • The protein encoded by this gene is a hyperpolarization-activated cation channel involved in the generation of native pacemaker activity in the heart and in the brain. The encoded protein is activated by cAMP and can produce a fast, large current. Defects in this gene were noted as a possible cause of some forms of epilepsy. [provided by RefSeq, Jan 2017]

GeneCards Summary for HCN2 Gene

HCN2 (Hyperpolarization Activated Cyclic Nucleotide Gated Potassium And Sodium Channel 2) is a Protein Coding gene. Diseases associated with HCN2 include Sinoatrial Node Disease. Among its related pathways are Sweet Taste Signaling and Transmission across Chemical Synapses. Gene Ontology (GO) annotations related to this gene include identical protein binding and voltage-gated potassium channel activity. An important paralog of this gene is HCN4.

UniProtKB/Swiss-Prot for HCN2 Gene

  • Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). Can also transport ammonium in the distal nephron. Produces a large instantaneous current. Modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages (By similarity).

Tocris Summary for HCN2 Gene

  • HCN (hyperpolarization-activated, cyclic nucleotide-gated) channels are members of the cyclic nucleotide-regulated channel family along with cyclic nucleotide-gated (CNG) channels. They are cationic channels that open under hyperpolarization.

Gene Wiki entry for HCN2 Gene

Additional gene information for HCN2 Gene

No data available for CIViC summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for HCN2 Gene

Genomics for HCN2 Gene

GeneHancer (GH) Regulatory Elements for HCN2 Gene

Promoters and enhancers for HCN2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH19J000589 Promoter/Enhancer 1.6 EPDnew Ensembl dbSUPER 650.7 +0.1 108 0.8 RB1 L3MBTL2 SP2 REST GATAD2B BCL11B ZNF148 SP1 SCRT2 VEZF1 HCN2 LOC100420586 GC19M000592 GC19P000592 GC19P000591 CDC34
GH19J000588 Enhancer 1.1 ENCODE dbSUPER 650.7 -1.6 -1577 0.2 ARID4B SIN3A ZNF2 ZNF48 GLIS2 ZNF143 RUNX3 SP3 SP5 MXD4 HCN2 GC19P000591 GC19P000592 BSG CDC34 GC19M000583
GH19J000718 Enhancer 1.5 FANTOM5 Ensembl ENCODE dbSUPER 14.1 +129.8 129801 3.1 ELF3 ARID4B BMI1 DNMT3B THRB ZNF48 RARA EGR1 SCRT2 ZNF143 HCN2 PALM FGF22 SHC2 C2CD4C GC19M000724
GH19J000631 Promoter/Enhancer 2 EPDnew Ensembl ENCODE 10.3 +43.4 43365 2.6 HDGF PKNOX1 ARNT ARID4B SIN3A DMAP1 YY1 ZNF766 E2F8 ZNF207 POLRMT LOC105372234 DAZAP1 STK11 MIER2 HCN2 ENSG00000261204 GC19P000611
GH19J000622 Enhancer 0.9 ENCODE dbSUPER 13.1 +34.1 34116 2.2 INSM2 KLF17 BACH1 ZIC2 FOS FOSL2 MAFK ZBTB8A MNT REST POLRMT HCN2 GC19P000611
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around HCN2 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the HCN2 gene promoter:
  • NRSF form 2
  • NRSF form 1
  • AP-1
  • AP-2alpha
  • AP-2alpha isoform 2

Genomic Locations for HCN2 Gene

Genomic Locations for HCN2 Gene
chr19:589,893-617,159
(GRCh38/hg38)
Size:
27,267 bases
Orientation:
Plus strand
chr19:589,893-617,159
(GRCh37/hg19)
Size:
27,267 bases
Orientation:
Plus strand

Genomic View for HCN2 Gene

Genes around HCN2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
HCN2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for HCN2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for HCN2 Gene

Proteins for HCN2 Gene

  • Protein details for HCN2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9UL51-HCN2_HUMAN
    Recommended name:
    Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 2
    Protein Accession:
    Q9UL51
    Secondary Accessions:
    • O60742
    • O60743
    • O75267
    • Q9UBS2

    Protein attributes for HCN2 Gene

    Size:
    889 amino acids
    Molecular mass:
    96950 Da
    Quaternary structure:
    • The potassium channel is composed of a homo- or heterotetrameric complex of pore-forming subunits. Heterotetramer with HCN1. Forms an obligate 4:4 complex with accessory subunit PEX5L. Interacts with KCNE2 (By similarity). Homotetramer.
    Miscellaneous:
    • Inhibited by extracellular cesium ions.

    Three dimensional structures from OCA and Proteopedia for HCN2 Gene

neXtProt entry for HCN2 Gene

Post-translational modifications for HCN2 Gene

  • Phosphorylation at Ser-668 by PRKG2 shifts the voltage-dependence to more negative voltages, hence counteracting the stimulatory effect of cGMP on gating.
  • Glycosylation at Asn407
  • Ubiquitination at isoforms=177
  • Modification sites at PhosphoSitePlus

Other Protein References for HCN2 Gene

ENSEMBL proteins:
REFSEQ proteins:

No data available for DME Specific Peptides for HCN2 Gene

Domains & Families for HCN2 Gene

Gene Families for HCN2 Gene

HGNC:
IUPHAR :
Human Protein Atlas (HPA):
  • Predicted membrane proteins
  • Transporters
  • Voltage-gated ion channels

Suggested Antigen Peptide Sequences for HCN2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9UL51

UniProtKB/Swiss-Prot:

HCN2_HUMAN :
  • The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
  • Belongs to the potassium channel HCN family.
Domain:
  • The segment S4 is probably the voltage-sensor and is characterized by a series of positively charged amino acids at every third position.
Family:
  • Belongs to the potassium channel HCN family.
genes like me logo Genes that share domains with HCN2: view

Function for HCN2 Gene

Molecular function for HCN2 Gene

UniProtKB/Swiss-Prot Function:
Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). Can also transport ammonium in the distal nephron. Produces a large instantaneous current. Modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages (By similarity).
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. cAMP binding causes a conformation change that leads to the assembly of an active tetramer and channel opening. Channel activity is modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages.
GENATLAS Biochemistry:
hyperpolarization-activated and cyclic nucleotide gated potassium channel 2,expressed in brain and heart (conduction tissues and contractile myocytes),pace-maker channel of the heart

Gene Ontology (GO) - Molecular Function for HCN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005216 ion channel activity IEA --
GO:0005222 intracellular cAMP activated cation channel activity IDA 10228147
GO:0005244 voltage-gated ion channel activity IEA --
GO:0005248 voltage-gated sodium channel activity IMP 22748890
GO:0005249 voltage-gated potassium channel activity IMP 22748890
genes like me logo Genes that share ontologies with HCN2: view
genes like me logo Genes that share phenotypes with HCN2: view

Animal Models for HCN2 Gene

MGI Knock Outs for HCN2:

Animal Model Products

  • Taconic Biosciences Mouse Models for HCN2

Clone Products

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for HCN2 Gene

Localization for HCN2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for HCN2 Gene

Cell membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for HCN2 gene
Compartment Confidence
plasma membrane 5
cytosol 2

Gene Ontology (GO) - Cellular Components for HCN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005886 plasma membrane TAS --
GO:0005887 integral component of plasma membrane IDA 10228147
GO:0008076 voltage-gated potassium channel complex TAS 9630217
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
genes like me logo Genes that share ontologies with HCN2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for HCN2 Gene

Pathways & Interactions for HCN2 Gene

genes like me logo Genes that share pathways with HCN2: view

Pathways by source for HCN2 Gene

1 BioSystems pathway for HCN2 Gene
3 Reactome pathways for HCN2 Gene
1 PharmGKB pathway for HCN2 Gene
1 KEGG pathway for HCN2 Gene
1 Qiagen pathway for HCN2 Gene
1 Cell Signaling Technology pathway for HCN2 Gene

Gene Ontology (GO) - Biological Process for HCN2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006811 ion transport IEA --
GO:0006813 potassium ion transport IEA --
GO:0006814 sodium ion transport IEA --
GO:0007267 cell-cell signaling TAS 9630217
GO:0034765 regulation of ion transmembrane transport IEA --
genes like me logo Genes that share ontologies with HCN2: view

No data available for SIGNOR curated interactions for HCN2 Gene

Drugs & Compounds for HCN2 Gene

(11) Drugs for HCN2 Gene - From: DrugBank, DGIdb, IUPHAR, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
ivabradine Approved Pharma Antagonist, Pore Blocker, Target, inhibitor 0
cyclic amp Experimental Pharma Target 0
Cyclic GMP Experimental Pharma Target 0
cilobradine Pharma Antagonist, Pore Blocker 0
Cs<sup>+</sup> Pharma Antagonist, Pore Blocker 0

(2) Additional Compounds for HCN2 Gene - From: HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Chloride ion
  • Chloride(1-)
  • Chlorine anion
  • CL(-)
  • Bertholite
  • Chloor
16887-00-6
sodium
  • Na(+)
  • Na+
  • SODIUM ion
7440-23-5
genes like me logo Genes that share compounds with HCN2: view

Transcripts for HCN2 Gene

mRNA/cDNA for HCN2 Gene

(1) REFSEQ mRNAs :
(5) Additional mRNA sequences :
(38) Selected AceView cDNA sequences:
(1) Ensembl transcripts including schematic representations, and UCSC links where relevant :

Unigene Clusters for HCN2 Gene

Hyperpolarization activated cyclic nucleotide-gated potassium channel 2:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for HCN2 Gene

No ASD Table

Relevant External Links for HCN2 Gene

GeneLoc Exon Structure for
HCN2
ECgene alternative splicing isoforms for
HCN2

Expression for HCN2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for HCN2 Gene

mRNA differential expression in normal tissues according to GTEx for HCN2 Gene

This gene is overexpressed in Brain - Putamen (basal ganglia) (x6.2), Brain - Spinal cord (cervical c-1) (x5.3), Brain - Caudate (basal ganglia) (x5.0), Brain - Substantia nigra (x4.8), Brain - Cortex (x4.7), and Brain - Nucleus accumbens (basal ganglia) (x4.6).

Protein differential expression in normal tissues from HIPED for HCN2 Gene

This gene is overexpressed in Frontal cortex (26.8), Retina (21.2), Platelet (10.6), and Spinal cord (10.3).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for HCN2 Gene



Protein tissue co-expression partners for HCN2 Gene

- Elite partner

NURSA nuclear receptor signaling pathways regulating expression of HCN2 Gene:

HCN2

SOURCE GeneReport for Unigene cluster for HCN2 Gene:

Hs.124161

mRNA Expression by UniProt/SwissProt for HCN2 Gene:

Q9UL51-HCN2_HUMAN
Tissue specificity: Highly expressed throughout the brain. Detected at low levels in heart.

Evidence on tissue expression from TISSUES for HCN2 Gene

  • Heart(4.3)
  • Nervous system(4.3)
genes like me logo Genes that share expression patterns with HCN2: view

No data available for Phenotype-based relationships between genes and organs from Gene ORGANizer for HCN2 Gene

Orthologs for HCN2 Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for HCN2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia LOC467640 33
  • 94.4 (n)
HCN2 34
  • 78 (a)
OneToOne
dog
(Canis familiaris)
Mammalia HCN2 34 33
  • 93.03 (n)
OneToOne
cow
(Bos Taurus)
Mammalia HCN2 34 33
  • 91.4 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia HCN2 34
  • 88 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Hcn2 33
  • 87.93 (n)
mouse
(Mus musculus)
Mammalia Hcn2 16 34 33
  • 87.39 (n)
platypus
(Ornithorhynchus anatinus)
Mammalia HCN2 34
  • 67 (a)
OneToOne
chicken
(Gallus gallus)
Aves HCN2 34 33
  • 84.59 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia HCN2 34
  • 63 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia hcn2 33
  • 76.49 (n)
zebrafish
(Danio rerio)
Actinopterygii hcn2b 34 33
  • 71.32 (n)
OneToMany
HCN2 (2 of 2) 34
  • 65 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta Ih 34 35
  • 27 (a)
OneToMany
wheat
(Triticum aestivum)
Liliopsida Ta.20011 33
sea squirt
(Ciona savignyi)
Ascidiacea -- 34
  • 53 (a)
ManyToMany
Species where no ortholog for HCN2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • worm (Caenorhabditis elegans)

Evolution for HCN2 Gene

ENSEMBL:
Gene Tree for HCN2 (if available)
TreeFam:
Gene Tree for HCN2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for HCN2: view image

Paralogs for HCN2 Gene

Paralogs for HCN2 Gene

(3) SIMAP similar genes for HCN2 Gene using alignment to 1 proteins:

  • HCN2_HUMAN

Pseudogenes.org Pseudogenes for HCN2 Gene

genes like me logo Genes that share paralogs with HCN2: view

Variants for HCN2 Gene

Sequence variations from dbSNP and Humsavar for HCN2 Gene

SNP ID Clin Chr 19 pos Variation AA Info Type
rs1060499863 likely-benign, not specified 590,191(+) C/T coding_sequence_variant, synonymous_variant
rs55978915 likely-benign, not specified 610,412(+) C/T intron_variant
rs1060499864 uncertain-significance, not specified 616,136(+) G/C coding_sequence_variant, missense_variant
rs1064796423 uncertain-significance, not specified 613,291(+) C/T coding_sequence_variant, missense_variant
rs201057562 uncertain-significance, not specified 610,392(+) G/A coding_sequence_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for HCN2 Gene

Variant ID Type Subtype PubMed ID
dgv134n111 CNV deletion 26073780
dgv1676n106 CNV deletion 24896259
dgv482e201 CNV deletion 23290073
dgv483e201 CNV deletion 23290073
dgv484e201 CNV deletion 23290073
dgv6174n54 CNV loss 21841781
esv1739089 CNV insertion 17803354
esv2658944 CNV deletion 23128226
esv2717746 CNV deletion 23290073
esv2717748 CNV deletion 23290073
esv2717749 CNV deletion 23290073
esv27631 CNV gain 19812545
esv3037 CNV loss 18987735
esv3361020 CNV duplication 20981092
esv3417596 CNV duplication 20981092
esv3643356 CNV loss 21293372
nsv1071484 CNV deletion 25765185
nsv1116526 OTHER inversion 24896259
nsv1142247 CNV tandem duplication 24896259
nsv428360 CNV gain 18775914
nsv470101 CNV loss 18288195
nsv577978 CNV gain 21841781
nsv828350 CNV loss 20364138
nsv953938 CNV deletion 24416366
nsv954667 CNV deletion 24416366

Variation tolerance for HCN2 Gene

Residual Variation Intolerance Score: 2.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.56; 86.07% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for HCN2 Gene

Human Gene Mutation Database (HGMD)
HCN2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
HCN2

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for HCN2 Gene

Disorders for HCN2 Gene

MalaCards: The human disease database

(1) MalaCards diseases for HCN2 Gene - From: HGMD and DISEASES

Disorder Aliases PubMed IDs
sinoatrial node disease
  • sa node
- elite association - COSMIC cancer census association via MalaCards
Search HCN2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for HCN2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with HCN2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for HCN2 Gene

Publications for HCN2 Gene

  1. Two pacemaker channels from human heart with profoundly different activation kinetics. (PMID: 10228147) Ludwig A … Biel M (The EMBO journal 1999) 2 3 4 22 58
  2. Augmented currents of an HCN2 variant in patients with febrile seizure syndromes. (PMID: 20437590) Dibbens LM … Petrou S (Annals of neurology 2010) 3 22 44 58
  3. Mutation analysis of the hyperpolarization-activated cyclic nucleotide-gated channels HCN1 and HCN2 in idiopathic generalized epilepsy. (PMID: 17931874) Tang B … Escayg A (Neurobiology of disease 2008) 3 22 44 58
  4. Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain. (PMID: 9630217) Santoro B … Tibbs GR (Cell 1998) 2 3 4 58
  5. Tetramerization dynamics of C-terminal domain underlies isoform-specific cAMP gating in hyperpolarization-activated cyclic nucleotide-gated channels. (PMID: 22006928) Lolicato M … Moroni A (The Journal of biological chemistry 2011) 3 4 58

Products for HCN2 Gene

Sources for HCN2 Gene

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